Objective: To construct the malignant transformation model of human bronchial epithelial (HBE) cell line by exposing to low level of sodium arsenite and determine if the nuclear factor E2 related factor 2 (Nrf2) signaling pathway is involved in this process.
Methods: HBE cells were continuously exposed to 2.5 micromol/L sodium arsenite and malignant transformation occurred as evidenced by the MTT assay, colony formation assay and cell migration assay. Western blot was used to evaluate the expression of Nrf2, quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (10-1) during sodium arsenite-induced transformation of HBE cells.
Results: MTT assay demonstrated that the proliferation of HBE cells was out of control with increasing passages of sodium arsenite exposure. In As-HBE-T25 and As-HBE-T50 cells, the cell invasion ability was 2.04 and 4.17 times than that in normal HBE cells and colony formation rate was 1.33% depedent manner (P < 0.5). Also, the expresion of QO1 and HO-1, downstream of Nrf2 target proteins, were also decreased with the expression of Nrf2.
Conclusion: The transformation of HBE cells induced by chronic exposure to sodium arsenite is mediated by decreased Nrf2 level and its downstream NQO1 and HO-1 protein, which subsequently promote the malignant proliferation.
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